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Many lipopolyplex (LPP) delivery systems struggle to achieve efficient nucleic acid release through the membrane fusion pathway. Herein, we developed a novel ternary lipopolyplex (LPP) platform of lipid\/HBPL\/mRNA LPPs by incorporating hyperbranched poly\u2010L\u2010lysine (HBPL) as a functional polymeric core. The highly branched architecture of HBPL enabled a unique balance between high mRNA encapsulation efficiency, efficient intracellular release, and exceptional colloidal stability, thereby overcoming a key limitation of conventional lipid nanoparticles. This platform primarily promoted cellular uptake through a membrane fusion mechanism in vitro, thereby achieving highly efficient cytoplasmic delivery, while the HBPL core enabled superior mRNA release compared to its linear\n                    <jats:italic>\u03b5<\/jats:italic>\n                    \u2010Polylysine (\n                    <jats:italic>\u03b5<\/jats:italic>\n                    \u2010PLL, hereafter referred to as PLL)\u2010based counterpart. These attributes collectively yielded high transfection efficiency across multiple cell lines, significantly enhanced dendritic cell (DC) maturation, and superior biocompatibility over a commercial transfection reagent. Efficient mRNA delivery to the lungs and spleen was also confirmed in vivo, with protein expression sustained even after 1 month of storage. By successfully integrating long\u2010term stability with high delivery efficiency, this HBPL\u2010based LPP platform represents a highly promising candidate for advancing mRNA therapeutics and vaccines.\n                  <\/jats:p>","DOI":"10.1002\/adhm.71571","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T05:40:39Z","timestamp":1786599639000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hyperbranched Polylysine\u2010Based Lipopolyplexes Enable Efficient mRNA Delivery With Long\u2010Term Storage Stability"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-1289-2208","authenticated-orcid":false,"given":"Huidi","family":"Meng","sequence":"first","affiliation":[{"name":"College of Engineers Zhejiang University  Hangzhou China"},{"name":"Zhejiang Engineering Research Center for Interface Technology of Medical Polymers and Devices Shaoxing Key Laboratory of Healthcare Materials and Application Technology and Center for Healthcare Materials Shaoxing Institute Zhejiang University  Shaoxing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingjie","family":"Fu","sequence":"additional","affiliation":[{"name":"College of Engineers Zhejiang University  Hangzhou China"},{"name":"Zhejiang Engineering Research Center for Interface Technology of Medical Polymers and Devices Shaoxing Key Laboratory of Healthcare Materials and Application Technology and Center for Healthcare Materials Shaoxing Institute Zhejiang University  Shaoxing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Liang","sequence":"additional","affiliation":[{"name":"Zhejiang Engineering Research Center for Interface Technology of Medical Polymers and Devices Shaoxing Key Laboratory of Healthcare Materials and Application Technology and Center for Healthcare Materials Shaoxing Institute Zhejiang University  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Organic Materials and Technologies MOE Key Laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and Engineering Zhejiang University  Hangzhou China"},{"name":"Dr. Li Dak Sum Yip Yio Chin Center for Stem Cell and Regenerative Medicine Zhejiang University  Hangzhou China"},{"name":"The State Key Laboratory of Transvascular Implantation Devices Zhejiang University  Hangzhou 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